The present invention relates generally to lipid emulsion systems. Specifically, the present invention relates to lipid emulsion systems for intravenous infusion.
It is known to intravenously infuse lipid emulsions into patients. Typically, lipid emulsions comprise: an aqueous environment; an emulsifier; and a glyceride oil component. Present commercial lipid emulsions, such as, for example, TRAVAMULSION, INTRALIPID, and LYPOSYN, utilize an excess amount of phospholipids as an emulsifier in their formulations. For example, these formulations typically have a phospholipid to glyceride oil ratio, by weight, of approximately 0.12 to 0.06. The excess phospholipids result in a fraction of the expected emulsion vesicles as well as a single and multilamellar liposome fraction.
As stated above, these lipid emulsions are designed to be infused into a patient. Because of the use of excess phospholipids, removal of the lipid emulsions from the blood stream may not proceed at a sufficiently fast rate. It is believed that removal of the emulsion particles from the blood stream is by a pathway having a half life (T 1/2) of up to approximately 1 hour. However, removal of the liposome particles from the blood stream is by another pathway, having an extremely long T 1/2 of 2 days. (See Untracht, S. H., Intravascular Metabolism of an Artificial Transporter of Triacylglycerols, Biochem Biophys Acta 711(1): 176-92, 1982. ) Because the liposome particles are removed from the blood stream via this second pathway that has a long T 1/2 hyperlipidemia is observed in many patients after parenteral lipid emulsion infusions. The inventor of the present invention believes that it is the liposomes, that use the longer T 1/2 pathway, that produce the hyperlipidemia observed in patients who receive lipid emulsion infusions.
Hyperlipidemia is a condition wherein the patient has too much lipid in his blood. This results in an increase in the risk of cardio-vascular disease, gastrointestinal disturbances, heptosplenomegaly, impaired hepatic function, anemia, thromobocytopenia, prolonged clotting time, spontaneous bleeding, and respiratory complications. This is especially true in neonates and infants, wherein hyperlipidemia is a dangerous condition that can cause respiratory failure. Indeed, many doctors will not prescribe lipid emulsions for neonates and infants due to the fear of hyperlipidemia and accompanying respiratory failure.